A phase 2 trial found that acalabrutinib monotherapy induced a complete or partial response among more than 50% of patients with relapsed or refractory (R/R) marginal zone lymphoma (MZL). These interim results were presented in a poster session at the 2022 ASCO Annual Meeting.

“MZL is a rare, indolent B-cell lymphoma that is considered incurable after recurrence. Similar to many B-cell malignancies, the pathway involved in the pathogenesis of MZL can be moderated through inhibition of Bruton tyrosine kinase (BTK). Acalabrutinib is a next-generation BTK inhibitor approved for other malignancies. It has previously demonstrated activity in MZL,” explained presenter Lihua Elizabeth Budde, MD, PhD, from City of Hope National Medical Center in Duarte, California.

For this proof-of-concept, open-label phase 2 study (ClinicalTrials.gov Identifier: NCT02180711), patients with confirmed MZL who had received 1 or more prior systemic therapies were treated with 100 mg acalabrutinib twice daily until disease progression or unacceptable toxicity. The primary efficacy outcome was the overall response rate.

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As of January 2022, 43 patients had received treatment for a median of 10 months (range, 0.3-38.6).

The study population was 60.5% male and the median age was 69 years (range, 42-84). The majority of the cohort, 53.5%, had an Eastern Cooperative Oncology Group performance status of zero; 44.2% had the extranodal MZL subtype, 30.2% the nodal subtype, and 25.6% the splenic subtype. Equal shares of patients had refractory disease (44.2%) and relapsed disease (44.2%), and the median number of prior lines of therapy was 1 (range, 1-4).

The overall response rate was 52.5%, with 12.5% of patients achieving complete responses and 40.0% partial responses. The complete response rate was highest among patients with nodal subtype (16.7%) followed by extranodal subtype (11.8%) and splenic subtype (9.1%). The partial response rate was highest among patients with extranodal subtype (52.9%) followed by splenic subtype (36.4%) and nodal subtype (25.0%).

Responses were maintained at 12 months among 75.8% of responders, with a median duration of response that was not estimable.

The overall survival rate at 12 months was 91.4%, and the progression-free survival rate at 12 months was 67.0%.

Any-grade treatment-emergent adverse events (TEAEs) occurred among 95.3% of patients; the most common were headache (32.6%), fatigue (27.9%), nausea (27.9%), and diarrhea (25.6%). TEAEs of grade 3 and higher occurred among 39.5% of patients, the most common TEAE was neutropenia (14.0%).

Among the events of clinical interest, the most frequent were infections (34.9%), bleeding (23.3%), cardiac events (14.0%), anemia (14.0%), and neutropenia and neutrophil count decrease (14.0%). There were no cases of atrial fibrillation or flutter, ventricular arrhythmias, or major bleeding.

This study was limited by the open-label design and the lack of a comparator arm.

Dr Budde concluded, “The results of this study support acalabrutinib as a safe alternative therapy and a feasible chemotherapy-free option for patients with R/R MZL.”

Disclosure: This research was supported by ALX Oncology and AstraZeneca. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Budde LE, Coleman M, Stevens D, et al. Acalabrutinib in patients with relapsed/refractory (R/R) marginal zone lymphoma (MZL): Results of a phase 2, multicenter, open-label trial. Presented at ASCO 2022; June 3-7, 2022. Abstract 7549.